Clinical Effectiveness of the Anti-Fibrotic Medications for Idiopathic Pulmonary Fibrosis.
Rationale: Since their approval, there has been no real-world or randomized trial evidence evaluating the effect of the anti-fibrotic medications pirfenidone and nintedanib on clinically important outcomes like mortality and hospitalizations.
Objectives: To evaluate the clinical effectiveness of the anti-fibrotic medications in patients with idiopathic pulmonary fibrosis.
Methods: Using a large United States insurance database, we identified 8098 patients with idiopathic pulmonary fibrosis between October 1, 2014 and March 1, 2018. A one-to-one propensity score matched cohort was created to compare those treated with anti-fibrotic medications (n=1255) to those not on treatment (n=1255). The primary outcome was all-cause mortality. The secondary outcome was acute hospitalizations. Subgroup analysis was performed to evaluate mortality differences by drug.
Measurements and main results: The use of anti-fibrotic medications was associated with a decreased risk of all-cause mortality (Hazard Ratio 0.77; 95% confidence interval, 0.62 to 0.98; p value=0.034). However, this association was present only through the first two years of treatment. There was also a decrease in acute hospitalizations in the treated cohort (Hazard Ratio 0.70; 95% confidence interval, 0.61 to 0.80; p value<0.001). There was no significant difference in all-cause mortality between patients receiving pirfenidone and those on nintedanib (Hazard Ratio 1.14; 95% CI, 0.79 to 1.65; p=0.471).
Conclusions: Among patients with idiopathic pulmonary fibrosis, anti-fibrotic agents may be associated with a lower risk of all-cause mortality and hospitalizations compared to no treatment. Future research should test the hypothesis that these treatments reduce early but not long-term mortality as demonstrated in our study.